ИСТИНА

A growing literature indicates that mitochondria are key participants in immune responses. Mitochondrial electron transport through oxidative phosphorylation machinery is an important source of cellular reactive oxygen species (ROS). Mitochondrial ROS are increasingly recognized as key regulator NF­κB, MAPKs, and IRF signaling pathways and therefore influence immune responses. In this work, the feasibility of mitochondria targeted antioxidant SkQ1based therapy for prevention ocular inflammation was demonstrated in vivo. Here we investigated the anti­inflammatory effect of SkQ1 on widely used for evaluating potential ocular anti­inflammatory compounds model of lipopolysaccharide (LPS)­induced uveitis in rabbits. It has been reported that LPS caused release of pro­inflammatory factors, such as tumor necrosis factor­α (TNF­α) and interlekin­6 (IL­6). As crucial inflammation mediators, TNF­α and IL­6 stimulates acute phase reaction of inflammation by influencing on oxidative stress, prostaglandins (PG) formation, leukocyte infiltration into the anterior segment (AS). We evaluated the effect of SkQ1 on ocular inflammation. At 24h after LPS injection, severe iris hyperemia and fibrinous pupillary membranes were observed. Compared to the LPS group SkQ1 pretreatment animals showed mild hyperemia and clear pupils. The histopathological changes in the AS of eyes were examined. Our results indicated in the LPS group histological evaluation revealed massive leukocyte infiltration into the AS. In the SkQ1 group the infiltrated leukocytes significantly decreased. Biochemical analyses of the AS showed that SkQ1 decreased LPS­induced IL­6, PGE2 and malondialdehyde production in the AS. In conclusion, SkQ1 prevents LPS­induced uveitis and the subsequent production of proinflammatory mediators, at least in part, by blocking mitochondrial ROS production. These effects may contribute to the SkQ1­mediated preventive effects on intraocular inflammatory diseases such as acute uveitis.